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(12) Patent Application Publication (10) Pub. No.: US 2006/0134109 A1 Gaitanaris Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2006/0134109 A1 Gaitanaris Et Al US 2006O134109A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0134109 A1 Gaitanaris et al. (43) Pub. Date: Jun. 22, 2006 (54) GPROTEIN COUPLED RECEPTORS AND in-part of application No. 60/461.329, filed on Apr. 9. USES THEREOF 2003. (75) Inventors: George A. Gaitanaris, Seattle, WA Publication Classification (US); John E. Bergmann, Mercer Island, WA (US); Alexander Gragerov, (51) Int. Cl. Seattle, WA (US); John Hohmann, La CI2O I/68 (2006.01) Conner, WA (US); Fusheng Li, Seattle, C7H 2L/04 (2006.01) WA (US); Linda Madisen, Seattle, WA (US); Kellie L. McIlwain, Renton, WA CI2P 2/06 (2006.01) (US); Maria N. Pavlova, Seattle, WA A 6LX 39/395 (2006.01) (US); Demitri Vassilatis, Seattle, WA C07K I4/705 (2006.01) (US); Hongkui Zeng, Shoreline, WA (52) U.S. Cl. ......................... 424/143.1: 435/6: 435/69.1; 435/320.1; 435/325; 530/350; (US) 536/23.5 Correspondence Address: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC (57) ABSTRACT 701 FIFTHAVE SUTE 63OO The present invention provides GPCR polypeptides and SEATTLE, WA 98104-7092 (US) polynucleotides, recombinant materials, and transgenic (73) Assignee: Nura Inc., Seattle, WA (US) mice, as well as methods for their production. The polypep tides and polynucleotides are useful, for example, in meth (21) Appl. No.: 10/527,265 ods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying com (22) PCT Fed: Sep. 9, 2003 pounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for (86) PCT No.: PCT/USO3/28226 treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified com Related U.S. Application Data pounds. The invention also provides diagnostic assays for (63) Continuation-in-part of application No. 60/409,303, detecting diseases or disorders associated with inappropriate filed on Sep. 9, 2002, and which is a continuation GPCR activity or levels. Patent Application Publication Jun. 22, 2006 Sheet 1 of 9 US 2006/0134109 A1 FIGURE esoGPCR Genes Class A Class A Class A Class A Class B group W6 GPR4s port grows angroup A9 orphangroup Ato Prs eras Rox orphangroup A P2Y10 Frust 2 orphan grouo A12 roR2 t 12 1. E. g te AS I s enga $8 M is a 21 M R A CR2 2 CCR3. ccR4 CCRs CCRs c CR cas MC1R 3 M GPR2 car 32 kJ CCRL ccR2 ceep2 KBR1 room it is dros H. D : anni TGig 24 h. '. 242 GPR1 72 H. 243 hit - ENRA 24 HA Ere 24S hu Erin a 2: 24s H.W. cars 247 hit 'Pas 24 HN 408 GPR12 249 wer 250 is H.M. GPRs 251 HM 7 K.M. tars a2 is wer as h pgrass H tire 25 3PR31, 25S H.A. PR as HM “cres as Ku : Patent Application Publication Jun. 22, 2006 Sheet 2 of 9 US 2006/0134109 A1 FIGURE 2 Eamily Class A (Cont) Tachykinin Orphan A9 Orexin Neuropeptide FF Neuropeptide Y Prokineticin2 CCK Orphan As Bombesin OrphanEndothelin A4 Angiotensin Hormone Bradykinin LGR orphan A2 Relaxin/NSL3 Wasopressin 8 Soratostain s opioidinociceptin SREB orphan Neuropeptide W Opsin orphan A8 FMLP O Malatonin Orphan A8 Anaphylatoxin Orphan A3 Leukotriene Galanin Sphingolipid 3 O McH Orphan A1 Cannabinoid Melanocortin ADPfluop-glucose PAF Prostanoid cysLT o Orphan A7 Orphan A11 Adrenoceptor a Orphan A10 dopamine Adrenocaptor A Purinoceptor Serotonin SPCLPC Dopamine as Adrieoneculin Sorolonin Proteinase activate Trace armine Eicosanoid Orphan A5 Adenosire Acetylcholine 2. Histamino orphan A2 Motilin, GIrwin Neuroterishn Neuromedinu Orphan A12 Family EMR Latrophilin glutarnate Proto-cadherin BA orphan 83 s' GAA Orphan 32 O Orphan B1 Class F/S Calcitonin Patent Application Publication Jun. 22, 2006 Sheet 3 of 9 US 2006/0134109 A1 FIGURE 3. i Patent Application Publication Jun. 22, 2006 Sheet 5 of 9 US 2006/0134109 A1 FIGURE 5. Patent Application Publication Jun. 22, 2006 Sheet 6 of 9 US 2006/0134109 A1 FIGURE 6A. FIGURE 6B. Patent Application Publication Jun. 22, 2006 Sheet 7 of 9 US 2006/0134109 A1 FIGURE 7A. FIGURE 7B. GPR85. SIH: TT GPR85 - Baseline Temperature 1. a G s E. ww. 3 o w d c C E G C d U > L O chd g o c O o Patent Application Publication Jun. 22, 2006 Sheet 8 of 9 US 2006/0134109 A1 FIGURE 8, PGR854 Conditioned Fear - Context Genotype Patent Application Publication Jun. 22, 2006 Sheet 9 of 9 US 2006/0134109 A1 FIGURE 9A. FIGURE 9B. GPR85-Ethanol Sensitivity GPR85 - Ethanol Tolerance A. VA V WW P 4. t V th U al ( Treatment day Genotype US 2006/0134109 A1 Jun. 22, 2006 G PROTEIN COUPLED RECEPTORS AND USES include: (a) polypeptides including a polypeptide sequence THEREOF having at least 90%. 95%, 97%, 98%, or 99% identity to a polypeptide listed in Table 2; (b) polypeptides that include REFERENCE TO TABLE SUBMITTED ON a polypeptide listed in Table 2; (c) polypeptides having at COMPACT DISC least 90%, 95%, 97%, 98%, or 99% sequence identity to a 0001 Pursuant to PCT Administrative Instruction S polypeptide listed in Table 2; and (d) polypeptides listed in 801(a), Table 35 is submitted herewith in triplicate on Table 2. compact disc as “50001.007WO3 Table 35.txt,” created on 0008 Polypeptides of the present invention also include Sep. 8, 2003 and having a size of 1,804 kB, hereby incor variants of the aforementioned polypeptides, including all porated by reference. allelic forms and splice variants. Such polypeptides vary from the reference polypeptide by insertions, deletions, and BACKGROUND OF THE INVENTION Substitutions that may be conservative or non-conservative, 0002 The invention relates to the fields of medicine and or any combination thereof. Particularly desirable variants drug discovery. are those in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 0003 Mammalian G protein coupled receptors (GPCRs) to 2, or from 2 to I amino acids are inserted, Substituted, or constitute a Superfamily of diverse proteins with thousands deleted, in any combination. of members. GPCRs act as receptors for a multitude of different signals. Chemosensory GPCRs (csGPCR) are 0009 Polypeptides of the present invention also include receptors for sensory signals of external origin that are polypeptides that include an amino acid sequence having at sensed as odors, pheromones, or tastes. Most other GPCRs least 30, 50, or 100 contiguous amino acids from any of the respond to endogenous signals, such as peptides, lipids, polypeptides listed in Table 2. Polypeptides of the invention neurotransmitters, or nucleotides. GPCRs falling in the latter are desirably biologically active or are antigenic or immu group are involved in numerous physiological processes, nogenic in an animal, especially in a human. including the regulation of neuronal excitability, metabo 0010. The polypeptides of the present invention may be lism, reproduction, development, hormonal homeostasis, in the form of the “mature' polypeptide, or may be a part of and behavior, and are differentially expressed in many cell a larger polypeptide such as a precursor or a fusion protein. types in the body. It is often advantageous to include an additional amino acid 0004) Of all currently marketed drugs, greater than 30% Sequence that contains Secretory or leader Sequences, pro are modulators of specific GPCRs. Only 10% of GPCRs sequences, sequences that aid in purification, for instance (excluding csGPCRs) are targeted by these drugs, empha multiple histidine residues, or an additional sequence for sizing the potential of the remaining 90% of the gene family stability during recombinant production. for the treatment of human disease. 0011 Polypeptides of the present invention can be pre 0005. Despite the importance of GPCRs in physiology pared in any suitable manner, for instance by isolation from and disease, the size of the GPCR superfamily is still naturally occurring sources, from genetically engineered uncertain. Analyses of genome sequences have generated host cells comprising expression systems, or by chemical markedly varied estimates (Venter, J. C. et al., Science 291, synthesis, using for instance automated peptide synthesizers, 1304-51 (2001); Lander, E. S. et al., Nature 409, 860-921 or a combination of Such methods. For example, polypep (2001); Takeda, S. et al., FEBS Lett 520, 97-101 (2002)). In tides of the invention may be produced by expressing in a addition, while most GPCRs are known to be selectively cell (e.g., a yeast, bacterial, mammalian, or insect cell) a expressed in Subsets of cells, the expression patterns of most vector containing a polynucleotide that encodes a GPCR of GPCRs are incomplete or unknown. Thus, there is a need for the invention under condition in which the polypeptide (e.g., GPCR polypeptides, polynucleotides, antibodies, genetic one listed in Table 2) is expressed. Means for preparing Such models, and modulating compounds for use in the treatment polypeptides are well understood in the art. and diagnosis of a wide variety of disorders and diseases. 0012. In another aspect, the invention features substan tially pure GPCR polynucleotides. Such polynucleotides SUMMARY OF THE INVENTION include: (a) polynucleotides that include a polynucleotide sequence having at least 90%. 95%, 97%, 98%, or 99% 0006 The present invention provides GPCR polypep sequence identity to a polynucleotide listed in Table 2; (b) tides and polynucleotides, recombinant materials, and trans polynucleotides that include a polynucleotide sequence hav genic mice, as well as methods for their production. The ing at least 90%, 95%, 97%, 98%, or 99% sequence identity polypeptides and polynucleotides are useful, for example, in to the reverse complement of polynucleotide listed in Table methods of diagnosis and treatment of diseases and disor 2; (c) polynucleotides that include a polynucleotide listed in ders.
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